WELCOME TO THE ANTIGEN-SPECIFIC REVOLUTION™
Want to better understand and treat disease? Look no further than antigens, the specific molecular-level targets seen by the adaptive immune system. It’s time to Be Specific™.
Whereas our genome is set from birth, the immune system is an ever-changing adaptive intelligence informed by infections, foods, injuries, microbes, and our environment – made up of hundreds of billions of independent immune cells competing to seek, destroy, and remember antigen targets across our lifetime.
Foods directly provide antigens and sculpt what grows in the microbiome.
The microbiome sculpts immunity via TLRs and cross-reactive antigens.
Infections & vaccines provide TLRs and prime immunity.
Genetics, sex, & family predispose us to certain types of immunity.
Activity & lifestyle determine stress hormones and alter tolerogenic DAMPs.
A lifetime of immune experiences drives the body to make about as many antibody clones as there are stars in the Milky Way – creating an antigen-specific antibody fingerprint more unique than the genome.
Evidence is growing that for everything from Alzheimer’s to cancer, the antigen-specific antibody fingerprint plays a major role in human disease. Discover what these antibodies target with ANTYGEN™ products and services by CDI Labs.
Explore the world’s most powerful antigen libraries.
Antibodies come in a variety of forms called isotypes. Depending on the isotype, antibodies can promote cell killing, protective immune tolerance, or help educate T cells. We can help you measure any of them.
Antibodies come in a variety of forms called isotypes. Depending on the isotype, antibodies can promote cell killing, protective immune tolerance, or help educate T cells. We can help you measure any of them.
Many of humanity’s greatest unsolved medical mysteries are increasingly recognized as being “inflammatory” conditions. And inflammatory often means antigen-specific.
We founded ANTYGEN™ because we believe there are undiscovered antigen-specific and isotype-restricted antibody responses involved in these conditions. And that once known — those targets can be used as biomarkers to both diagnose disease and predict treatment outcomes. Some of these discoveries may even lead to new drugs and vaccines to treat or even prevent cancer, dementia, ageing, and more.
Technical overview of the antibody fingerprint.
A significant fraction of the entire human proteome is targeted by a very unique fingerprint of baseline autoantibodies in healthy individuals [1]. This landscape of autoantibodies is very specific to the individual person, can remain stable for many years, and contains unique features reported in association with cancer, autoimmunity, infection, and neurologic conditions [1–8].
Baseline autoantibodies can directly manipulate immune signaling to have dramatic associations with clinical outcomes. A survey of AIRE-deficient patients reported in Cell demonstrated that some patients harbored unique high-affinity neutralizing autoantibodies to type 1 interferons – especially IFNα [3]. Those patients with the naturally occurring IFNα neutralizing autoantibodies were protected from type-1 diabetes – a major complication of AIRE-deficiency [3]. This study demonstrates that major changes in global immunity can be created by natural antibodies that inadvertently target and manipulate immunologic pathways.
Additionally, IgG autoantibody may aid in priming antigen-specific anti-tumor CD8+ T cells, sculpting the T cell repertoire to approximately mirror background antibody. This was clearly demonstrated in a clinical paper where patients receiving anti-EGFR (Cetuximab®) antibody developed new CD8+ T cell responses to EGFR peptides through increased antigen-uptake and cross-presentation by antigen-presenting cells via Fc receptors [9]. In a mouse model, animals had stronger baseline IgG antibody signals to neoantigen peptides than their wild-type counterpart peptides – and were more likely to develop MHCI-restricted CD8+ T cell responses to peptide and live tumor if those antigens had stronger baseline IgG antibody signals [10]. Together, these data suggest that some features of T cell immunity – including CD8+ immunity – may be indirectly observable via antibodies as a surrogate.
Antibodies can directly help kill tumor cells via antibody-dependent cell-mediated cytotoxicity (ADCC) – directly impacting therapeutic outcomes. Most clearly visible via therapeutic antibody therapies such as anti-HER-2 (Trastuzumab®), ADCC is antibody-bound Fc-receptor directed killing of tumor cells – often aided by macrophages, monocytes, eosinophils, or natural killer cells directed via Fc receptors. This process is well established, varies in strength across antibody isotypes, and can be strongly directed against cancer by isotypes such as IgE that are less commonly screened for in cancer studies [11].
Mouse studies have long demonstrated that different IgG subtype responses result in dramatically different outcomes for cancer [12]. Analogous effects are recognized in humans with dramatically different antibody response outcomes under variances in IgG response subtypes, Fc receptor binding, and immune checkpoint environments [13]. In the clinic, there are demonstrations that baseline autoantibody fingerprints performed using ANTYGEN™ HuProt can predict side effects to anti-CTLA4 and anti-PD1 checkpoint blockade prior to treatment [14].
References:
- Nagele EP, Han M, Acharya NK, DeMarshall C, Kosciuk MC, Nagele RG. Natural IgG Autoantibodies Are Abundant and Ubiquitous in Human Sera, and Their Number Is Influenced By Age, Gender, and Disease. Tsokos GC, editor. PLoS ONE. 2013;8:e60726.
- Larman HB, Zhao Z, Laserson U, Li MZ, Ciccia A, Gakidis MAM, et al. Autoantigen discovery with a synthetic human peptidome. Nature Biotechnology. 2011;29:535–41.
- Meyer S, Woodward M, Hertel C, Vlaicu P, Haque Y, Kärner J, et al. AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies. Cell. 2016;166:582–95.
- Graff JN, Puri S, Bifulco CB, Fox BA, Beer TM. Sustained Complete Response to CTLA-4 Blockade in a Patient with Metastatic, Castration-Resistant Prostate Cancer. Cancer Immunology Research. 2014;2:399–403.
- Gnjatic S, Ritter E, Büchler MW, Giese NA, Brors B, Frei C, et al. Seromic profiling of ovarian and pancreatic cancer. Proceedings of the National Academy of Sciences. 2010;107:5088–5093.
- Wongkulab P, Wipasa J, Chaiwarith R, Supparatpinyo K. Autoantibody to Interferon-gamma Associated with Adult-Onset Immunodeficiency in Non-HIV Individuals in Northern Thailand. Rottenberg ME, editor. PLoS ONE. 2013;8:e76371.
- Anderson KS, Sibani S, Wallstrom G, Qiu J, Mendoza EA, Raphael J, et al. Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer. Journal of Proteome Research. 2011;10:85–96.
- Miersch S, Bian X, Wallstrom G, Sibani S, Logvinenko T, Wasserfall CH, et al. Serological autoantibody profiling of type 1 diabetes by protein arrays. Journal of Proteomics. 2013;94:486–96.
- Srivastava RM, Lee SC, Andrade Filho PA, Lord CA, Jie H-B, Davidson HC, et al. Cetuximab-Activated Natural Killer and Dendritic Cells Collaborate to Trigger Tumor Antigen-Specific T-cell Immunity in Head and Neck Cancer Patients. Clinical Cancer Research. 2013;19:1858–72.
- Hulett TW, Jensen SM, Wilmarth P, Reddy AP, et al. Coordinated responses to individual tumor antigens by IgG antibody and CD8+ T cells following cancer vaccination. 2018;14.
- Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, et al. Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells. European journal of immunology. 2003;33:1030–1040.
- Nimmerjahn F, Ravetch JV. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science. 2005 Dec 2; 310(5753): 1510–1512. doi: 10.1126/science.1118948.
- Teige I, Mårtensson L, Frendéus BL. Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy–Focus on FcγRIIB. Frontiers in Immunology. 2019. 10;481. https://www.frontiersin.org/article/10.3389/fimmu.2019.00481 doi:10.3389/fimmu.2019.00481
- Gowen MF, Giles KM, Simpson D, Tchack J, Zhou H, Moran U, et al. Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors. Journal of Translational Medicine [Internet]. 2018 [cited 2018 Nov 4];16. Available from: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1452